This is a National stage entry under 35 U.S.C. xc2xa7371 of Application No. PCT/JP00/05655 filed Aug. 24, 2000; the disclosure of which is incorporated herein by reference.
The present invention relates to an immunopotentiating composition and to a composition accelerating the production of interferon-xcex3.
The skin and mucous membrane boundaries between the body and the outside world, and particularly the intestinal and other mucous membranes of the digestive tract, come into contact with many foreign bodies including viruses, bacteria, parasites, disease antigens and food antigens. Therefore, the skin and mucous membranes have immune systems which protect the body by keeping out such foreign bodies. One immune substance which acts to keep out such foreign bodies is immunoglobulin A (IgA). IgA plays an important role in neutralizing toxins of bacteria or viruses, controlling adhesion of bacteria to tissue, and suppressing allergies caused by food antigens. Production of IgA involves the lymphocytes of the Peyer""s patch, a lymphatic tissue of the intestines.
When the immune functions of the biological protective systems of the digestive tract mucous membranes are depressed, foreign microorganisms colonize the digestive tract and proliferate, causing digestive tract infections, bacterial diarrhea and the like and resulting in such symptoms as fever, vomiting, diarrhea and abdominal pain. Immune function depression may also be caused by anorexia due to overwork or stress, for example.
Young children, the elderly and people in a weakened condition are particularly vulnerable to external pathogens because their immune systems are depressed. Consequently, substances which act to accelerate production of IgA and maintain it at high levels would be beneficial for such individuals and for the aforementioned digestive tract infection sufferers, particular if administration were in the form of a drink or other foodstuff.
However, there is currently no effective prophylactic or therapeutic drug which acts to accelerate IgA production in cases of depressed gut immune function and intestinal infections. Treatments of bacterial diarrheal diseases are currently limited to fluid infusions for dehydration and administration of antibiotics.
Consequently, the object of the invention is to provide a new digestive immunopotentiating composition for prevention and/or treatment of such intestinal infections and the like, and particularly such a composition in the form of a drink or other foodstuff.
After extensive research aimed at attaining this object, the inventors accomplished the invention upon making the novel discovery that lactosucrose exhibits the desired immunopotentiating effect in humans, and that the administration of lactosucrose can treat and prevent the digestive tract infections and the like.
The invention provides an immunopotentiating composition comprising lactosucrose together with a carrier.
The inventors also found the novel fact that production of interferon-xcex3(IFN-xcex3) is accelerated by administration of such a composition.
Consequently, the invention provides a composition accelerating the production of IFN-xcex3 comprising lactosucrose together with a carrier.
The compositions of the invention must contain lactosucrose (hereunder referred to as xe2x80x9cLSxe2x80x9d) as an active ingredient. As used here, the term xe2x80x9clactosucrosexe2x80x9d indicates the well-known substance of the following chemical formula, having the chemical name O-xcex2-D-galactopyranosyl-(1xe2x86x924)-O-xcex1-D-glucopyranosyl-(1←2)-xcex2-D-fructofuranoside. 
LS can be manufactured by various methods. Such methods include for example the method of applying Aerobacter-derived levansucrase to a solution containing sucrose and lactose as described in Japanese Examined Patent Publication No. S57-58905, the method of applying a fungus of the genus Sporobolomyces, such as for example Sporobolomyces singularis, or an extract thereof to a solution containing sucrose and lactose as described in Japanese Unexamined Patent Publication No. S64-85090, or the method of applying a fungus of the genus Rahnella, such as for example Rahnella aquatilis, or an extract thereof to a solution containing sucrose and lactose as described in Japanese Unexamined Patent Publication No. H2-35095.
A reaction mixture comprising mainly LS obtained by the aforementioned methods or purified LS prepared therefrom may be used in the composition of the invention.
LS is also known as a vital nutrient (glycogen) which is essential for selective growth of Bifidobacterium in the intestine.
The proportion of LS in the composition of the invention is normally selected from the range of about 0.5 to about 70 g/100 g or preferably about 5 to about 30 g/100
There are no particular limits on the form of the immunopotentiating composition or composition accelerating the production of IFN-xcex3 of the present invention so long as it can be administered orally or ingested. The composition can be provided in various forms including block, liquid, syrup or powder. More specific examples of forms that can be used include foodstuffs such as liquid or powdered sweeteners, beverages such as soft drinks, milk drinks and carbonated drinks, and snacks such as breads, cookies and candies as well as health foods, and medicinal preparations such as bulk powders, powders, liquids, suspensions, tablets and effervescent preparations and the like.
Of these, drinks and effervescent preparations are particularly desirable.
The above-mentioned forms of the composition of the invention may be produced by formulating the active ingredient LS together with food carriers or pharmaceutically acceptable drug carriers suited to the various forms. Food carriers include for example such edible additives as fillers, sweeteners, other carbohydrates, vitamins, flavors and colorings.
More specifically, if for example the composition of the present invention is in food form, considering that a daily allowance (effective dose) of LS is about 1 to about 30 g, the composition is prepared from LS together with suitable food carriers so that the effective dose can be easily ingested. A typical example of a food form is a drink, which can be prepared in the form of an aqueous solution containing 0.5-70 g/100 ml or preferably 5-30 g/100 ml of the active ingredient. The pH of such a drink can also be adjusted to about 4.0 to about 6.5 or preferably about 4.5 to about 6.0 using a pH regulator or buffer or the like.
Typical examples of such pH regulators or buffers include weak acids such as citric acid, tartaric acid, malic acid, lactic acid and carbonic acid, and salts thereof such as sodium citrate, ammonium citrate, sodium tartrate, sodium malate, sodium lactate, calcium lactate, sodium carbonate and sodium hydrogencarbonate. Sodium hydrogenphosphate can also be used as the pH regulator or buffer. These acids or salts thereof can be used either individually or in combinations of two or more. The formulating amount thereof is selected from a range conducive to the above-mentioned pH range of product beverage, but may generally be no greater than about 2% by weight or preferably about 0.05 to about 0.3% by weight of the composition.
Various carbohydrates, sweeteners and other additives can also be added to the composition of the invention when it is in the form of such a drink or other foodstuff, as they are to ordinary beverages and the like. Examples of carbohydrates include glucose, fructose and other monosaccharides; maltose, sucrose and other disaccharides; dextrin, cyclodextrin and other polysaccharides (other than LS); xylitol, erythritol, sorbitol and other sugar alcohols; and sugar esters and the like. Examples of sweeteners include natural sweeteners (Rebaudioside A and other stevia extracts, sormatin, glycyrrhizin and the like) and synthetic sweeteners (saccharin, aspartame and the like). The formulating amount of such carbohydrates or sweeteners is generally no more than about 15% or preferably about 13% by weight of the resulting beverage.
One or two or more of the following additives, for example, may also be added as necessary when formulating the composition of the invention as a foodstuff. Such additives include for example grapefruit, apple, orange, lemon, pineapple, banana, pear and other fruit juices (either concentrated or powdered juices or the like); vitamins and provitamins (retinol palmitate, bisbentiamine, riboflavin, pyridoxine hydrochloride, cyanocobalamin, sodium ascorbate, nicotinamide, calcium pantothenate, folic acid, biotin, cholecalciferol, calcium bitartrate, tocopherol, beta carotene and other water-soluble and fat-soluble vitamins); flavors (lemon flavor, orange flavor, grapefruit flavor, vanilla essence and the like); amino acids, nucleic acids and salts thereof (glutamic acid, sodium glutamate, glycine, alanine, aspartic acid, sodium aspargin, inosinic acid and the like); dietary fibers (polydextrose, pectin, xanthan gum, gum arabic, alginic acid and the like); and minerals and trace elements (sodium chloride, sodium acetate, magnesium sulfate, potassium chloride, magnesium chloride, magnesium carbonate, calcium chloride, dipotassium phosphate, monosodium phosphate, calcium glycerophosphate, sodium ferrous citrate, ammonium ferric citrate, iron citrate, manganese sulfate, copper sulfate, sodium iodide, potassium sorbate, zinc, manganese, copper, iodine, cobalt and the like).
The composition of the invention is prepared by mixing the aforementioned ingredients. There are no particular limits on the method of preparation, and the ingredients may all be mixed in one step as necessary, or when oily and aqueous ingredients are concurrently used the oily ingredients may first be dissolved in a suitable oily vehicle, and then emulsified with an aqueous solution of the aqueous ingredients with the aid of an emulsifier. This emulsification process may be carried out by ordinary methods using ordinary emulsifying dispersion equipment such as a homomixer or high-pressure homogenizer or the like, either in a pass-through or circulating system. The ingredients are ordinarily mixed or emulsified at room temperature, but a heating process may also be employed. The resulting composition of the invention is then packed in suitable containers and sterilized by ordinary methods such as pasteurization, sterile filtration or the like to produce a product.
The composition of the invention can also be processed into effervescent products which can be dissolved or dispersed in water, such as tablets, granules, powder or capsules or the like. Such effervescent products are prepared using sodium hydrogencarbonate and/or sodium carbonate as foaming agents along with a neutralizer. Possible neutralizers include for example citric acid, tartaric acid, fumaric acid, ascorbic acid, lactic acid, malic acid and the like. The proportions of the foaming agent and neutralizer in the total ingredients are preferably be selected from the range of 8-60% by weight of effervescing agent and 10-70% of neutralizer. Such effervescent products can be prepared according to ordinary methods such as direct powder compression or dry or wet granulation compression, optionally with the addition of a suitable amount of potassium carbonate.
There are no particular limits on the ingested or administered dose of the composition of the invention, which is established judiciously according to the intended use or the age, sex, body weight or severity of illness of the intended user, and other factors. When the composition of the invention is in solid form, about 1 to about 30 g of the active ingredient per dose is normally ingested at one time, preferably after dissolution in 30-200 ml of water. When the composition of the invention is in drink or other liquid form, about 30 to about 200 ml is to be taken at a single time. The daily ingested or administered amount of the composition of the invention is preferably such that about 0.5 to about 70 g or preferably about 1 to about 30 g or more preferably about 3 to about 20 g of the active ingredient contained therein is ingested or administered. This ingested or administered amount can be achieved by taking the aforementioned solid or drink form several times a day.
Upon oral administration or ingestion, the composition of the invention can produce immunopotentiating or IFN-xcex3 production accelerating effects, enhancing the biological defence mechanisms (immune functions) of the digestive tract and effectively preventing and treating intestinal infections and the like.